The purpose of the present application is to study the genetic and environmental factors causing age-associated autoimmunity in human beings. Using newly developed in vitro tissue culture techniques, we have begun to analyze for the first time age-associated changes in the frequency and expression of autoreactive B cells. In lymphocyte cultures from human cord blood, middle aged adults, adults older than 70 years, and patients with autoimmune disease, we are studying 1) the frequency of B cells reactive with IgG, thyroglobulin and DNA, as compared to the appearance of autoantibody in the serum, 2) the avidity, specificity, and heterogeneity of the antibodies in the four groups, and 3) the role of regulatory T cells an naturally occurring polyclonal B cell activators in triggering autoantibody production. Through these experiments we expect to delineate those controlling factors in age-associated autoimmunity which might be successfully prevented or modulated.